Elucidating Serotonergic Mechanisms Regulating Cardiovascular Recovery After Grafting Embryonic Raphe Neurons into the Injured Rat Spinal Cord

阐明将胚胎中缝神经元移植到受伤大鼠脊髓后调节心血管恢复的血清素能机制

基本信息

  • 批准号:
    10231367
  • 负责人:
  • 金额:
    $ 3.65万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-07-01 至 2022-03-04
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Spinal cord injury (SCI) at the 6th thoracic level (T6) or above often results in the loss of supraspinal regulation over cardiovascular function. This dysfunction manifests as abnormal resting hemodynamics and the development of orthostatic hypotension and autonomic dysreflexia (AD). Collectively, these irregularities mark cardiovascular dysfunction as one of the leading causes of morbidity and mortality among the population. Although there are current pharmacological and preventative measures in place to mitigate these issues, they lack long-term efficacy and do not address the underlying loss of supraspinal connectivity. Recently, we discovered grafting raphe nuclei-derived neural progenitors/stem cells (RN-NPCs) after SCI partially restores hemodynamic regulation. More specifically, we found that the graft restores connectivity between raphe nuclei cell populations and sympathetic preganglionic neurons in the spinal cord. Moreover, silencing serotonergic receptor 5HT2A resulted in the loss of functional recovery. Therefore, we hypothesize that functional recovery after grafting is centrally mediated through supraspinal and intraspinal serotonergic mechanisms. In Aim 1, we will graft RN-NPCs into rats sustaining a T4 crush injury and measure cardiovascular output including resting hemodynamics, and AD frequency and severity. Subsequently, we will reinjury the rats above the transplant site and reevaluate all hemodynamic parameters. This will determine if functional restoration is contingent on supraspinal connectivity with the graft. In Aim 2, we will employ chemogenetic techniques to silence serotonergic neurons of the host caudal raphe nuclei after RN-NPC grafting to identify if supraspinal serotonergic regulation of cardiovascular function has been reestablished. In Aim 3, we will use the same chemogenetic tools to silence graft-derived serotonergic neurons, elucidating if these neurons facilitate hemodynamic restoration. We will also administer serotonergic and noradrenergic receptor antagonists to examine which spinal receptors are involved in reestablishing cardiovascular regulation. Collectively, these results will provide guidance for potential clinical translation to mitigate hemodynamic dysfunction after SCI.
项目总结/文摘

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Cameron T Trueblood其他文献

Cameron T Trueblood的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

相似海外基金

The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
  • 批准号:
    EP/Z000920/1
  • 财政年份:
    2025
  • 资助金额:
    $ 3.65万
  • 项目类别:
    Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
  • 批准号:
    FT230100276
  • 财政年份:
    2024
  • 资助金额:
    $ 3.65万
  • 项目类别:
    ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
  • 批准号:
    MR/X024261/1
  • 财政年份:
    2024
  • 资助金额:
    $ 3.65万
  • 项目类别:
    Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
  • 批准号:
    DE240100388
  • 财政年份:
    2024
  • 资助金额:
    $ 3.65万
  • 项目类别:
    Discovery Early Career Researcher Award
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
  • 批准号:
    2232190
  • 财政年份:
    2023
  • 资助金额:
    $ 3.65万
  • 项目类别:
    Continuing Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
  • 批准号:
    2337595
  • 财政年份:
    2023
  • 资助金额:
    $ 3.65万
  • 项目类别:
    Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
  • 批准号:
    23K17514
  • 财政年份:
    2023
  • 资助金额:
    $ 3.65万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
Analysis of thermoregulatory mechanisms by the CNS using model animals of female-dominant infectious hypothermia
使用雌性传染性低体温模型动物分析中枢神经系统的体温调节机制
  • 批准号:
    23KK0126
  • 财政年份:
    2023
  • 资助金额:
    $ 3.65万
  • 项目类别:
    Fund for the Promotion of Joint International Research (International Collaborative Research)
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
  • 批准号:
    2842926
  • 财政年份:
    2023
  • 资助金额:
    $ 3.65万
  • 项目类别:
    Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
  • 批准号:
    NC/X001644/1
  • 财政年份:
    2023
  • 资助金额:
    $ 3.65万
  • 项目类别:
    Training Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了